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Opposing roles of TGFβ and BMP signaling in prostate cancer development

SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate canc...

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Autores principales: Lu, Xin, Jin, Eun-Jung, Cheng, Xi, Feng, Shan, Shang, Xiaoying, Deng, Pingna, Jiang, Shan, Chang, Qing, Rahmy, Sharif, Chaudhary, Seema, Lu, Xuemin, Zhao, Ren, Wang, Y. Alan, DePinho, Ronald A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795781/
https://www.ncbi.nlm.nih.gov/pubmed/29352019
http://dx.doi.org/10.1101/gad.307116.117
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author Lu, Xin
Jin, Eun-Jung
Cheng, Xi
Feng, Shan
Shang, Xiaoying
Deng, Pingna
Jiang, Shan
Chang, Qing
Rahmy, Sharif
Chaudhary, Seema
Lu, Xuemin
Zhao, Ren
Wang, Y. Alan
DePinho, Ronald A.
author_facet Lu, Xin
Jin, Eun-Jung
Cheng, Xi
Feng, Shan
Shang, Xiaoying
Deng, Pingna
Jiang, Shan
Chang, Qing
Rahmy, Sharif
Chaudhary, Seema
Lu, Xuemin
Zhao, Ren
Wang, Y. Alan
DePinho, Ronald A.
author_sort Lu, Xin
collection PubMed
description SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity of TGFβ–BMP signaling and illuminate potential therapeutic targets for prostate cancer.
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spelling pubmed-57957812018-06-01 Opposing roles of TGFβ and BMP signaling in prostate cancer development Lu, Xin Jin, Eun-Jung Cheng, Xi Feng, Shan Shang, Xiaoying Deng, Pingna Jiang, Shan Chang, Qing Rahmy, Sharif Chaudhary, Seema Lu, Xuemin Zhao, Ren Wang, Y. Alan DePinho, Ronald A. Genes Dev Research Communication SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity of TGFβ–BMP signaling and illuminate potential therapeutic targets for prostate cancer. Cold Spring Harbor Laboratory Press 2017-12-01 /pmc/articles/PMC5795781/ /pubmed/29352019 http://dx.doi.org/10.1101/gad.307116.117 Text en © 2018 Lu et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Lu, Xin
Jin, Eun-Jung
Cheng, Xi
Feng, Shan
Shang, Xiaoying
Deng, Pingna
Jiang, Shan
Chang, Qing
Rahmy, Sharif
Chaudhary, Seema
Lu, Xuemin
Zhao, Ren
Wang, Y. Alan
DePinho, Ronald A.
Opposing roles of TGFβ and BMP signaling in prostate cancer development
title Opposing roles of TGFβ and BMP signaling in prostate cancer development
title_full Opposing roles of TGFβ and BMP signaling in prostate cancer development
title_fullStr Opposing roles of TGFβ and BMP signaling in prostate cancer development
title_full_unstemmed Opposing roles of TGFβ and BMP signaling in prostate cancer development
title_short Opposing roles of TGFβ and BMP signaling in prostate cancer development
title_sort opposing roles of tgfβ and bmp signaling in prostate cancer development
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795781/
https://www.ncbi.nlm.nih.gov/pubmed/29352019
http://dx.doi.org/10.1101/gad.307116.117
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